She co-wrote the theme song to A Different World, with Bill Cosby and Stu Gardner, and co-performed the song for the first season. In A Different World, Lewis appeared for the first five of the six-season run as Jaleesa Vinson (later Vinson-Taylor) from 1987 to 1992. Although her character was married to another of the main characters on the show, her character disappeared from A Different World without explanation, like Chuck Cunningham of Happy Days.

In Hangin' with Mr. Cooper, Lewis appeared in the first of the five seasons as Robin Dumars. She did not appear on the two shows concurrently — she left A Different World to star in Hangin' with Mr. Cooper. She and Holly Robinson Peete, along with R&B quartet En Vogue, performed the theme song for Season 1 of Mr. Cooper.